tbuckley/cabot-search huggingface dataset:
Racial differences in survival and healthcare resource utilization among Medicaid-insured adults with metastatic castration-resistant prostate cancer.
Authors: Maral DerSarkissian, Deepshekhar Gupta, Jasmina Ivanova, Alexander Niyazov, Enrico Zanardo, Tracy Guo, Jingru Wang, Mei Sheng Duh, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2023)

29 Background: Prostate cancer (PC) disproportionately affects Black or African American (BAA) men in the United States (US), but racial disparities in outcomes are not well understood. This study analyzed racial disparities in OS, healthcare resource utilization (HRU), and PC treatments in Medicaid-insured metastatic castration resistant PC (mCRPC) patients. Methods: This retrospective longitudinal cohort study evaluated de-identified data from the Centers for Medicare and Medicaid Services 100% Medicaid data files from 01/01/2010 – 12/31/2018. The study included adult patients with a diagnosis of PC and metastasis, and a claim for at least one of the following drugs prior to 9/30/2018, which is specific to mCRPC (date defined index): ≥1 claim for cabazitaxel, mitoxantrone, enzalutamide, radium-223, or sipuleucel-T, ≥1 claim for abiraterone acetate before June 2017, ≥1 claim for docetaxel at least 90 days after initiation of hormone therapy, or evidence of castration resistance. Patients were required to be continuously enrolled for ≥6 months pre-index (i.e., baseline period) and ≥3 months post-index. Outcomes were assessed from the index date to the earliest of end of continuous enrollment, data availability, or death. A multivariable Cox proportional hazards model of OS, and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index, baseline HRU, baseline PC treatments, and clinical characteristics. Results: The study included 1,095 mCRPC patients (320 [29%] White [W], 278 [25%] BAA, 190 [17%] Hispanic [H], 307 [28%] Other races [O]). H had the highest mean age of 69 years, followed by 68 years for O, and 63 years for both W and BAA. Median unadjusted OS was 46.7 months in H, 40.5 months in BAA, 35.3 months in O, and 32.3 months in W. After adjustment, H had significantly lower risk of death vs. W (hazard ratio [95% confidence interval (CI)]: 0.62 [0.42, 0.90]) and BAA had comparable survival to W (0.85 [0.62, 1.16]). BAA had significantly fewer PC-related outpatient (OP) visits vs. W (adjusted incidence rate ratios [IRR] [95% CI]: 0.67 [0.48, 0.93]), but significantly more PC-related emergency room (ER) visits (5.03 [2.03, 12.47]) per patient per year. Race cohorts differed in the proportions of patients treated with novel hormonal therapy (70% W, 63% BAA, 58% H, 67% O) and chemotherapy use (29% BAA, 26% H, 24% W, 19% O). Conclusions: Among Medicaid-insured adult mCRPC patients, H were more likely to live longer than W patients, while BAA and W patients had similar OS. BAA patients had a higher rate of PC-related ER visits but fewer PC-related OP visits as compared to W, showing differential use of PC-related healthcare resources.
Detection of intraductal carcinoma of the prostate (IDCP) cases focusing on high-grade prostatic intraepithelial neoplasia (PIN) findings regarding invasive carcinoma of the prostate.
Authors: Ryuta Watanabe, Naoya Sugihara, Reina Kono, Osuke Arai, Toshio Kakuda, Terutaka Noda, Kenichi Nishimura, Tetsuya Fukumoto, Noriyoshi Miura, Mie Kurata, Yuki Miyauchi, Riko Kitazawa, Michael C Haffner, Tadahiko Kikugawa, Takashi Saika
Journal: Journal of Clinical Oncology (2023)

379 Background: Intraductal carcinoma of the prostate (IDCP) is a pathological pattern that involves atypical cells proliferating within the normal gland where basal cells are preserved. These exhibit cribriform morphology, a finding associated with poor prognosis. In addition to the TMPRSS2-ERG fusion gene, TP53, RB1, and PTEN deletions, and SPOP and HRR gene mutations, such as a BRCA mutations, are frequently detected in patients with IDCP. The National Comprehensive Cancer Network (NCCN) guidelines suggest that early genetic testing should be considered. However, IDCP recognition is notably low, and diagnosis requires skill. Methods: We selected 98 cases with "prostate cancer with high-grade prostatic intraepithelial neoplasia (PIN) in the background" by referring to the pathology reports of cases who underwent total prostatectomy for prostate cancer at our hospital between November 2011 and November 2021. Twelve cases were narrowed down to those that were considered suggestive of IDCP based on the pathology reports and reviewed by three pathologists to determine the presence of IDCP. These were additionally reviewed by three pathologists for the presence or absence of IDCP and a gene test of prostatectomy specimens was submitted for the relevant cases to determine the presence or absence of HRR gene mutations. Results: Five of the twelve cases were determined to be IDCP positive. The Gleason score of background prostate cancer was 4+3 in 3 cases, 4+4 in 1 case, and 4+5 in 1 case. Median postoperative follow-up was 37 months (22- 45 months); 3 of the 5 patients had no recurrence, 1 had recurrence at 2 years and 3 months resulting in additional local radio therapy (RT), and 1 patient died of other causes. Pathology genetic testing identified HRR-related genetic abnormalities, including BRCA mutations. Conclusions: We were able to establish IDCP cases from past high-grade PIN cases. As a number of HRR gene mutations of unknown pathological significance were detected, IDCP cases could be retrieved from past cases and genetic abnormalities could be identified efficiently. The findings of the study provide a possible approach to diagnose prostate cancer cases with genetic mutations at an early stage.
Analysis of <i>TP53</i> gain of function mutations in metastatic castration-resistant prostate cancer.
Authors: Patrick L Sweeney, Sree M Lanka, Albert Jang, Kanika Gupta, Sydney Caputo, Crystal Casado, Minqi Huang, Olivia Pocha, Maddie Hawkins, Alexandra Lieberman, Jennifer Schwartz, Ellen B. Jaeger, Patrick Miller, Pedro C. Barata, Jodi Lyn Layton, Brian E. Lewis, Elisa M. Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2023)

246 Background: TP53, an oncogene implicated in the development of many malignancies, is commonly altered in mCRPC. Gain-of-function mutations in TP53 confer increased oncogenic properties of this gene and play a role in mCRPC. The goal of this study was to characterize somatic TP53 mutations, specifically gain-of-function mutations, in the ctDNA of mCRPC patients in the context of prior therapies. Methods: A retrospective analysis of mCRPC patients at Tulane Cancer Center between 2015-2022 was performed. All patients had ctDNA testing performed with the Guardant360 multigene panel assay. Clinical annotation including initial diagnosis, staging, treatment history, and family history were obtained. TP53 mutations were classified based on existing published functional studies and/or in silico evaluation. Statistical analyses were performed with Fisher's exact and Chi-squared tests where appropriate. Results: 338 mCRPC patients with ctDNA testing were included in this analysis. 76 patients had no prior treatment with either abiraterone or enzalutamide, while 262 patients had been treated with abiraterone and/or enzalutamide. Somatic TP53 mutations were similar in frequency between those with or without abiraterone/enzalutamide pretreatment; 46% (35/76) of patients in the abiraterone/enzalutamide naïve subset had a somatic TP53 mutation, compared to 41% (108/262) of patients previously treated with abiraterone and/or enzalutamide. Only 9% (7/76) of abiraterone/enzalutamide naïve patients had a TP53 gain-of-function mutation, compared to 19% (49/262) of patients previously treated with one or both drugs ( p = 0.05). The most common type of TP53 mutation was loss-of-function. There were no significant associations between TP 53 mutations and occurrence of other common mutations. Conclusions: mCRPC patients with prior treatment of abiraterone and/or enzalutamide were significantly more likely to have a gain-of-function TP53 mutation. Further studies are needed to investigate therapeutic implications of these findings.
Heterogeneity in physician and patient preferences for the treatment of renal cell carcinoma: Evidence from latent class analysis.
Authors: Caroline Vass, Cathy Anne Pinto, Kelley Myers, Kentaro Imai, Cooper Bussberg, Rituparna Bhattacharya, Shawna R Calhoun, Christine Poulos
Journal: Journal of Clinical Oncology (2023)

661 Background: To inform shared decision-making, it is important to learn how patients or physicians trade off the features of adjuvant treatments and whether there is heterogeneity within preferences. Methods: An online discrete-choice experiment survey was administered to patients with physician-confirmed renal cell carcinoma (RCC) and physician-defined intermediate high/high risk of recurrence and physicians who treat such patients. Hypothetical treatment choices were defined by median disease-free survival (DFS); 5-year overall survival (OS) rate; mode and frequency of administration; need for concomitant daily pill; treatment duration; and the risks of severe diarrhea, fatigue, and dizziness. After making an adjuvant treatment choice, respondents were presented with the opportunity to opt out of treatment. Patient and physician choice data were analyzed separately using latent class (LC) models, which identify clusters within patients and physicians making similar choices. Each class’ preference weights were used to calculate the conditional relative attribute importance. Results: LC analysis identified three classes among the 250 patients (% respondents) that placed greater relative importance on: 1) 5-year OS and opting into treatment (37.5%), 2) median DFS and opting into treatment (26.9%), and 3) treatment duration and opting out of treatment (35.5%) (Table). Among the 250 physicians, the LC analysis identified three classes that placed greater relative importance on: 1) 5-year OS and recommending treatment (37.5%), 2) median DFS and recommending treatment (37.8%), and 3) not recommending treatment (24.7%). Additionally, each LC analysis showed that the other treatment attributes evaluated were less important, but the importance varied by LC (Table). Conclusions: Heterogeneity in physician and patient preferences for RCC adjuvant therapy was found, highlighting a need for shared decision-making. Discordance within patients and physicians in the propensity to opt out of adjuvant treatment suggests patient-physician dialogue is important. [Table: see text]
Radium-223 for mCRPC, a real-world experience study from 7 Galician medical centers.
Authors: Urbano Anido Herranz, Ovidio Fernandez Calvo, Sara Martinez Breijo, Natalia Fernández Núñez, Zulema Nogareda Seoane, Miguel Garrido Pumar, Javier Casas, Gloria Muñiz Garcia, Paula Portela Pereira, Antonio Gomez Caamaño, Daniel Pérez Fentes, Lucía Santomé, Gerardo Huidobro Vence, Aurea Molina Díaz, Ana Medina, Juan Ruiz Bañobre, Sergio Vázquez Estévez
Journal: Journal of Clinical Oncology (2023)

96 Background: Radium-223 represents an option for symptomatic metastatic castration-resistant prostate cancer (mCRPC) after demonstrated an overall survival improvement in the ALSYMPCA trial. Radium-223 real-life experiences are scarce, particularly after the results of the ERA-223 trial. To describe Radium-223 outcomes in real life practice, and specifically those related with bone health, sequence of treatment, and prognostic factors. Methods: Multicenter retrospective study of a cohort of 143 patients with mCRPC treated with Radium-223 in either the second line or third line of therapy or beyond in the context of routine clinical practice between 11 March 2013 and 26 July 2022, in seven Galician hospitals. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Between March 11, 2013, and July 26, 2022, 143 patients were enrolled from 5 Galician hospitals. With a median follow-up of 9.68 months. All patients signed an informed consent form agreeing to participate in this observational study, that was approved by the Galician Ethics Committee, registration code 2018/282. Results: Baseline patient and disease characteristics are summarized. Median follow-up was 9.68 months. Median overall survival (OS) was 12 months (95% CI 9.7 – 16.0). Best OS outcomes were achieved in second and third line, 18 months (95% CI 12.0 – 26.0) and 9.4 months (95% CI 8.0 – 12.0) months, respectively. Among those baseline clinic-analytical factors analyzed, only alkaline phosphatase level &gt;354 UI/L was correlated with a worse OS (HR 2.56 (95% CI 1.39 – 4.72; p=0.003) and the number of cycles of Radium-223 received (HR 0.63 (95% CI 0.54 – 0.73; p&lt;0.001) were prognostic factors for Radium-223. Importantly, ninety-nine of patients (80%) were treated with bone-targeted therapy for bone metastases with no OS differences (p=0.66). Conclusions: In our study, Radium-223 efficacy was consistent with previously reported. Best efficacy was achieved in the second or third line of therapy, independently of docetaxel use. Patients with high baseline alkaline phosphatase had worse OS. Few patients presented skeletal-related events, which could be explained by an adequate use of bone-targeted therapy (zoledronic acid or denosumab). [Table: see text]
Association of inflammation and depression in renal cell carcinoma.
Authors: Benjamin Schmeusser, Adil Ali, Dattatraya H Patil, Eric Midenberg, Benjamin Petrinec, Mehmet Asim Bilen, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2023)

658 Background: Patients with cancer experience depression at higher rates, which is associated with worse outcomes and quality of life. In renal cell carcinoma (RCC) specifically, depression is particularly prevalent. Aside from the emotional distress of a cancer diagnosis, a biologic basis for cancer associated depression is inflammation, which is highly associated with RCC as well as worse outcomes. Here, we aim to assess the association between inflammation and major depression, measured by a score of 10+ on the Patient Health Questionnaire (PHQ-8), in patients undergoing nephrectomy for nonmetastatic RCC. Methods: A retrospective review of prospectively administered PHQ-8 surveys in patients that underwent nephrectomy for nonmetastatic RCC was conducted. Patients with available preoperative PHQ-8 within 180 days before surgery were included. Association of major depression on PHQ-8 with patient/tumor characteristics were determined by Generalized chi-square test or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. Multivariable logistic regression was used to determine variables significantly associated with major depression on PHQ-8, including pre-operative C-Reactive Protein (CRP) independently and combined with American Joint Committee on Cancer (AJCC) staging for RCC. Results: 224 patients were analyzed, with 67% being male. Median age and BMI was 64 and 29.0, respectively. 65.2% of patients were white, and 28.6% were black. Histologically, most patients had clear cell RCC (67.4%). AJCC staging was 52.2% stage I, 5.36% stage II, and 42.41% stage III. 30.4% had an elevated CRP (&gt;10mg/L). Median PHQ-8 score was 4, with 42 (18.8%) of patients screening positive for major depression on PHQ-8 (10+). Multivariable regression models showed elevated CRP alone (OR 2.74, 95% CI 1.02-7.40, p=0.047) and in-combination with AJCC stage I-II (OR=8.13, 95% CI 1.99-33.27, p=0.004) and III (OR=4.82, CI 1.11-20.88, p=0.035) as a predictor of major depression on PHQ-8. Conclusions: In this study of patients with nonmetastatic RCC, elevated CRP (&gt;10mg/L) was an independent predictor of major depression on PHQ-8. [Table: see text]
Impact of vaccination against SARS-CoV-2 on the risk of hospital admission and death among infected patients with urologic cancers: A population-based study in northern Italy.
Authors: Lucia Fratino, Michele Gobbato, Elena Clagnan, Martina Taborelli, Stefania Del Zotto, Federica Toffolutti, Ivana Burba, Francesca Tosolini, Joseph Polimeni, Diego Serraino
Journal: Journal of Clinical Oncology (2023)

205 Background: Background: Hospital admission and death of infected cancer patients were investigated according to SARS-CoV-2 vaccination status. Methods: Population-based observational study on 1874 SARS-CoV-2 infected patients with prostate (n=1276), kidney (n=327), and bladder (n=271) cancers. Hazard ratios (HR) and their 95% confidence intervals (CI), adjusted for sex and age, were computed to assess the risk of hospital admission and death of unvaccinated patients as compared to vaccinated ones. Results: 24.5% of patients with prostate, 26.9% with kidney and 29.5% with bladder cancer were unvaccinated. As compared to vaccinated ones, a statistically significant excess risk of hospital admission emerged for unvaccinated ones with prostate (HR=3.33, 95% CI: 2.50-4.55), and kidney (HR=4.35, 95% CI: 2.33-8.33) cancer. The 312 unvaccinated prostate cancer patients were also at a nearly 3-fold higher risk of death than vaccinated ones (HR=2.98, 95% CI:1.89-4.70). Conclusions: Study findings stress the importance of SARS-CoV-2 vaccines in reducing hospital admission and death in patients with urologic cancers, particularly prostate cancer.
Cardiovascular and thromboembolic events associated with intense neoadjuvant androgen deprivation therapy followed by prostatectomy in patients with localized prostate cancer: A meta-analysis of clinical trials.
Authors: Eduardo Felicio Campos, Camila Bragança Xavier, Marcello Moro Queiroz, Nildevande Firmino Lima, Denis L. Jardim, Diogo Assed Bastos, Eder Nisi Ilario, Rafael Ferreira Coelho, William Carlos Nahas
Journal: Journal of Clinical Oncology (2023)

341 Background: Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients (pts). However, data regarding complications of the intense hormone therapy and surgical complications are scarce. The phase III trial PROTEUS testing ARSIs plus ADT added an amendment for thrombotic prophylaxis in the perioperative setting. We conducted a systematic review and meta-analysis to evaluate cardiovascular (CV) and thromboembolic (TE) adverse events (AEs) during neoadjuvant and perioperative intervals. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42022344104). A comprehensive search of PubMed, Embase, and Scopus databases and conference abstracts was performed from January 2010 to June 2022. Eligible studies include randomized and single-arm trials testing ARSIs prior to prostatectomy which adequately reported safety data regarding TE and CV AEs, peri-operative complications, and mortality during therapy. DerSimon and Laird method for random effects model was performed to estimate the pooled incidence (PI) of events with 95% confidence interval (95% CI). Heterogeneity was tested with I2 value. Results: 8 RCTs and 3 single-arm phase II trials comprising 674 pts were included (674 pts for CV and TE AEs and 499 for perioperative complications). Neoadjuvant regimen was classified as monotherapy with ADT (21 pts), ARSIs (100 pts), combination therapy with ADT + ARSI (338 pts), or ADT + ARSI + ARSI (215 pts). PI of all grade TE was 3.2% (95% CI, 1.6% – 4.8%, I2 = 0.0%, p = 0.92); TE incidence during perioperative period was 3.9% (95% CI, 1.6 – 6.1%, I2 = 0.0%, p = 0.67). 7 deaths were reported, with a PI of 3.0% (95% CI, 0.7–5.3%, I2 = 0.0%, p = 0.98). 2 of the mortality AE were considered treatment-related within perioperative interval. Incidence of hypertension grade 3-5 was 8.9% (95% CI, 5.2–12.7%, I2= 51.6%, p = 0.02). Incidence measures per regimen are described. Conclusions: CV and TE events associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 3.9% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting. [Table: see text]
Evaluation of the safety and effectiveness of cryoablation in the treatment of renal angiomyolipoma related to tuberous sclerosis complex: The Cryo-TSC.
Authors: Eiji Kashiwagi, Takashi Hatano, Kanichiro Shimiz, Atsushi Takamoto, Koji Tomita, Takahiro Osawa, Yusuke Sakuhara, Fumiya Hongo, Tatsuya Hirota, Yasuhiro Ushijima, Yoshiki Asayama, Jun Miki, Fumiaki Kiyomi, Shin Egawa, Yasutomo Nasu, Nobuo Shinohara, Osamu Ukimura, Shuji Nakano, Yasuaki Arai, Masatoshi Eto
Journal: Journal of Clinical Oncology (2023)

669 Background: Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease. Approximately 60%–80% of patients with TSC have bilateral angiomyolipoma (AML). Cryotherapy is one treatment option for renal tumors, but the safety and efficacy of cryotherapy for TSC–AML is not clear. We planned this study to establish the safety and efficacy of cryotherapy for TSC–AML. Methods: This was an open-label, single-arm phase II study to evaluate the safety and efficacy of cryotherapy for TSC–AML of 4 cm or less in diameter in patients at least 16 years old. The exclusion criteria were an inability to withdraw from mTOR inhibitor and failure to maintain rest during cryotherapy. mTOR inhibitors were withdrawn at least 7 days prior to cryotherapy and discontinued during the study period. Cryotherapy was performed using Cryohit (Galil Medical LTD, USA). Safety was assessed at 1, 2, 6, and 9 months after cryotherapy, and efficacy was assessed at 3 and 9 months after cryotherapy. The efficacy of cryotherapy was evaluated according to the modified RECIST or RECIST criteria. The primary endpoint was the disease control rate, and secondary endpoints included the overall response rate, safety, renal function, quality of life, and need for additional treatment. Results: The disease control and overall response rates were 100% and 93.3%, respectively. After 9 months of follow-up, the median creatine level was slightly increased by 0.06 mg/dL. Quality of life was stable, and no additional treatment was needed. Three Grade 3 adverse events (hematuria, chronic kidney disease, and aspartate aminotransferase elevation) were observed in three patients. Conclusions: Cryoablation is a safe and effective treatment option for TSC–AML. Clinical trial information: jRCTs072200039 .